The effects of ergot alkaloid poisoning are mainly attributed to ergopeptin ergovalence; However, transport across ruminant gastric membranes is much higher with intermediate lysergyl compounds than with ergopeptins, suggesting that ergot intermediate alkaloids may also play an important role (Hill et al., 2001). On 1 January 2022, a new EU regulation will enter into force setting limits for ergot sclerotia and ergot alkaloids. These rules apply to a wide range of goods that are both manufactured in EU Member States and imported into EU Member States. Rye ergot poisonings (criminal and suicidal) were (and are) rare. Cases in which the autopsy proved death by poisoning with this raw drug were usually associated with attempted abortion. One such case was reported in 1864 [18]. The victim – a young unmarried woman – had all the clinical signs of ergot poisoning before her death – yellow skin, vomiting, headache, dry and irritated throat, and intestinal hyperemia [18]. Death occurred due to the aforementioned gangranosus ergotism. Other research showed that she consumed the tincture or ergot and essential oil of pennyroyal (Mentha pulegium L.) for 11 weeks [18].
The latter substance has been used as an abortifacient since ancient Greek times [19]. In recent decades, ergot sorghum has become a global threat. Losses of up to 80% in India and 25% in Zimbabwe have been reported (Bandyopadhyay et al., 1998). Probably due to its ability to produce airborne secondary conidia, it is C. africana which has emerged worldwide as the dominant pathogen of sorghum ergot and C. Sorghi has been almost completely replaced in India (Pažoutováet al., 2000). In the 19th century, the treatment of a fibrous tumor of the uterus was considered beyond the reach of medicine. One of the most problematic symptoms associated with this disease is excessive uterine bleeding and hypertrophy. Rye ergot medications have worked by removing (excreting) polyps or intramural tumors [12]. Dr.
Byford used a liquid extract of ergot (half a spoonful for three weeks; oral and sometimes hypodermic) in this treatment. As a result of therapy, the tumor was expelled and the uterus was reversed. The surgeon had to remove the remaining fibroids. In some cases, the pain during treatment was unbearable and therefore treatment had to be stopped before the expected therapeutic effect was achieved. At that time, two main compounds were used in the treatment of fibrous tumors of the uterus – aqueous extract of ergot of Wernich and aqueous extract of ergot of Squibb [12,13]. The situation is somewhat different with the sclerotia of Claviceps purpurea (Fr.) Tul. (Ergot) – a source of unknown origin and unknown ancient history. Over the centuries, this medicinal mushroom has been closely associated with gynecology and obstetrics.
LSD has always been made from lysergic acid, which is made from ergotamine or ergonovine, substances derived from an ergot fungus on rye, or lysergic acid amide, a chemical found in Morning Glory seeds. Ergot grass diseases caused by members of the genus Claviceps have had a severe impact on human history and agriculture, causing devastating epidemics. However, ergot alkaloids, the toxic components of Claviceps sklerotia, have been widely used (and abused) as medicines, and effective biotechnological processes have been developed for their in vitro production. Molecular genetics has provided detailed information on the genetic basis of ergot alkaloid biosynthesis and has opened up prospects for the design of new alkaloids and the improvement of production strains; It also revealed the refined infection strategy of this biotrophic pathogen, paving the way for better control. Nevertheless, claviceps remains an important pathogen worldwide and a source of potential new drugs for diseases of the central nervous system. As mentioned above, ergot was used as a raw drug until the 19th century. In the 20th century, individual alkaloids were extracted and described. Ergotoxin was discovered and described in 1906 as a unique chemical compound. This condition continued until 1943, when individual alkaloids were isolated.
Another alkaloid, ergotamine, was isolated by Stoll in 1918. Lysergic acid and isolysergic acid were described in 1934 and 1936 respectively. In 1935, another alkaloid was discovered – ergometrine [24,25]. The last time ergot poisoning occurred on a large scale in Europe was in 1771 in Westphalia, Hanover and Lauenburg, where in some villages only 5 out of 120 people survived [3]. It is also suggested that ergot may be responsible for the famous “choreography” (dance plague), while medieval European villagers fell into an involuntary dance trance [3]. The history of ergot is often marked by secrecy and secrecy, not least because its use has been associated with hallucinations and subsequent miscarriages. Local knowledge about ergot depends largely on its legal and economic use. In the case of abortions and miscarriages, ergot was considered illegal because of moral opposition to its use to harm women`s fertility. In the 20th century, the cultivation of ergot on Canadian grain threatened to poison livestock farms and undermine Canada`s reputation as a grain-producing country. As Canada faces a different regulatory future when it comes to psychedelics, it may be time to learn more about our own herbal medicines and how local communities have interpreted their value. Claviceps fungi (especially Claviceps purpurea) produce several distinct compounds grouped together as ergot alkaloids; The 12 regulated compounds include ergotamine, ergometrine and α-ergosine. Moulds affect a variety of species of grasses and small grains, with rye being the most common agricultural host.
British doctors were more cautious – they appreciated the effect of ergot, but they observed that the use of ergot during pregnancy and childbirth was associated with a higher infant mortality rate. In addition to the use of ergot in obstetrics, attempts have also been made to use C. Purpurea in amenorrhea [4]. In addition to dmaW, seven enzyme-coding eas genes were functionally analyzed by gene digestion and analysis of C. purpurea P1 intermediates. These include four non-ribosomal peptide synthetase (NRPS) genes, lpsA1/A2, lpsB and C. Biochemical evidence has shown that the final steps in ergopeptin synthesis in C. purpurea include a complex of two interacting NRPS (a new discovery in fungi): d-lysergylpeptidylsynthetase 2 (LPS2), which catalyzes lysergic acid activation, and LPS1, which forms the tripeptide radical (Fig. 3B; Riederer et al., 1996). Functional analysis showed that both lpsA1 and lpsA2 encode LPS1 enzymes: LPS1-1, which is required for the synthesis of the main P1 alkaloid, ergotamine, and LPS1-2 for ergocryptine synthesis (Haarmann et al., 2008; Tudzynski et al., 1999). The lpsC gene probably encodes a monomodular NRPS enzyme that catalyzes the formation of ergonovine (= ergometrine), an ergopeptin with a side chain of a single amino acid (I.
Ortel and U. Keller, FU Berlin, personal communication). Thus, this set of NRPS genes encodes a very flexible natural combinatorial system unique in eukaryotes: activated lysergic acid formed by LPS2 can be used as a receptor for the addition of several peptide units, which explains the high variability of the spectrum of ergot peptide alkaloids in C. purpurea strains. Ergotamine, which is sold under the brand names Cafergot (with caffeine) and Ergomar, among others, is an ergopeptin and is part of the ergot alkaloid family; It is structurally and biochemically closely related to ergolines. [4] It has structural similarity to several neurotransmitters and has biological activity as a vasoconstrictor. In 1814, Dr. Henry S. Waterhouse experienced difficulties during childbirth [9]. The patient reported vaginal bleeding and narrowing of the lower abdomen. Then she began to lose consciousness and began to bite her tongue.
In the hours that followed, the doctor observed alarming contractions of the muscles of his limbs, back, abdomen, neck and lower jaw [11]. Conventional medications of the time, such as opium tincture and asafoetida tincture (Ferula assa-foetida L.), did not stop the progression of symptoms [9].